Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
Project description:Even though autoimmune diseases are heterogeneous, believed to result from the interaction between genetic and environmental components, patients with these disorders exhibit reproducible patterns of gene expression in their peripheral blood mononuclear cells. A portion of this gene expression profile reflects family resemblance rather than the actual presence of an autoimmune disease. Here we wanted to identify that portion of this gene expression pattern that is independent of family resemblance and determine if it is a product of disease duration, disease onset, or other factors. By increasing the number of autoimmune samples in our analysis and employing supervised clustering algorithms, we identified 100 genes whose expression profiles are shared in individuals with various autoimmune diseases but are not shared by first-degree relatives of individuals with autoimmune disease or by controls. Individuals with early disease (1 yr after onset) and established disease (10 yr after onset) exhibit a near identical expression pattern suggesting that this unique profile reflects disease onset rather than disease duration. supervised gene expression profiling were performed to a cohort sample pool: control individuals(8), unaffected family members of autoimmune diseases patients (8), and individuals with autoimmune diseases (54). we try to identify a gene expression signatures that were exclusively associated with autoimmune diseases but not infulenced by genetic components
Project description:Variation in individuals' adaptive immune response is believed to influence susceptibility to complex diseases in humans. The genetic basis of such variation is poorly understood. We measured gene expression from resting and activated CD4+ T cells derived from the peripheral blood of healthy individuals. We activated the primary T cells with anti-CD3/CD28 beads. We collected peripheral blood from each human donor. We isolated peripheral blood mononuclear cells by Ficoll, and negatively selected for CD4+ T cells using RosettaSep. We then either left cells unstimulated or stimulated them with beads conjugated with anti-CD3 and anti-CD28. Cells from 15 individuals were harvested at up to 3 time points (0hr, 4hr or 48hr), lysed and RNA isolated to be profiled on microarray.
Project description:Low density neutrophils (LDN) co-purify with mononuclear cells during density-gradient separation of peripheral blood. LDN are rarely detected in healthy individuals but appear in the peripheral blood (PB) of patients with inflammatory diseases, malignancies and in individuals treated with granulocyte colony-stimulating factor (G-CSF). Using human G-CSF mobilized LDN, this study reveals that LDN are transcriptionally, proteomically and metabolically distinct from other neutrophils. Single Cell RNAseq analysis reveals that LDN from these donors comprise one major population, with multiple interrelated transcriptional states, representing the continuum of neutrophil maturation. LDN can engage both glycolysis and mitochondrial respiration to meet energy demands, which affords increased metabolically flexibility in the nutrient perturbed tissue environments found in tumours and inflammatory diseases. This study also identifies upregulated expression of CD98, a transporter for branch chain and aromatic amino acids, as a cell surface marker for LDN in peripheral blood. CD98 may contribute to the functional properties of LDNs and represents a useful phenotypic marker.
Project description:This project analyzes peripheral blood profiles of controls and patients of 14 different diseases, all collected, measured, and analyzed using exactly the same SoP. Since miRNAs are known to be valuable diagnostic markers we asked whether respective patterns of patients can be detected in peripheral blood samples rather than in biopsies. The project aimed at an impoved understanding of complex profiles rather than single markers. Thus, a high-throughput technique was necessary, profiling all known miRNAs integratively and combining different diseases to achieve a high degree of specificity. A total of 454 samples was screened, containing patients with different cancer types (lung cancer, melanoma, prostate cancer, wilms tumors, tumor of stomach, pancreatic cancer, ovarian cancer), autoimmune diseases (multiple sclerosis), cardiovascular (acute myocardial infarction), and chronic inflammatory diseases (sarcoidosis, periodontitis, pancreatitis, chronic obstructive pulmonary diseases), as well as healthy control individuals. Please note that each miRNA has been measured in at least seven replicates and the median of the replica has been computed.
Project description:CD24Fc is a recombinant fusion protein consisting of the extracellular domain of mature human CD24 linked to the human immunoglobulin G1 (IgG1) Fc domain. Preclinical studies have demonstrated that CD24Fc provide therapeutic effect for autoimmune diseases and graft-vs-host diseases. These studies prompted clinical development of CD24Fc for immunological diseases. As the first-in-human (FIH) study, CD24Fc was tested in a phase I, randomized, double-blind, placebo-controlled, single ascending dose study for safety and pharmacokinetics in healthy people. For global assessment of CD24Fc activity on host immune system, we collected the peripheral blood mononuclear cells (PBMC) from human subjects in CD24Fc phase I clinical study and performed RNA-sequencing for PBMC samples. We found that CD24Fc treatment significantly reduced the transcripts of genes encoding pattern recognition receptors, inflammatory cytokines, chemokines and their receptors.